PB1906: HYPOMETHYLATING AGENT PLUS LOW DOSE VENETOCLAX – A CHEMOTHERAPY-FREE INDUCTION OF ACUTE MYELOID LEUKEMIA TO ACHIEVE COMPLETE REMISSION IN PATIENTS UNFIT FOR CHEMOTHERAPY
Authors: Karthik Kumar, Sashi Kant Singh, Jhasaketan Nayak, Adamya Gupta, Paras Satadeve, Ronanki Kavya, Pratibha Singh, Aishwarya Muralidharan, Arjun K, Reshma Benson, Gaurav Dhingra, Uttam Kumar Nath
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Breakthrough in managing acute myeloid leukemia(AML) came in 1973 after the results of “3 + 7” combination induction regimen (daunorubicin and cytosine arabinoside) was published. For five decades and till now, it has been the standard induction treatment of medically fit patients. Mortality of “3 + 7” induction is 16% in fit patients. So, decision of induction in unfit patients is challenging. The introduction of HMA plus Venetoclax combination is a new breakthrough in managing AML. This combination has shown a 54 to 67% CR rate in various studies. Here we present our one-year experience with HMA plus low dose venetoclax plus azoles as induction therapy in medically unfit patients. Aims: To evaluate the response rate and grade 3-4 adverse event of two cycles of induction therapy with hypomethylating agent and low dose venetoclax in medically unfit patients. Methods: Retrospectively enrolled all the newly diagnosed and relapsed AML patients from January 2022 to January 2023 who were medically unfit for intensive chemotherapy. Patient were categorized medically unfit if Eastern Cooperative Oncology Group (ECOG) performance status was ≥ 3 or charlson comorbidity index (CCI) was ≥3. All the patients were treated with two cycles of induction therapy with Injection Decitabine 20mg/m2 × 5 days, Azacytidine 75mg/m2 × 7 days, and Tablet Venetoclax 100 mg/day for 28 days every 28 days’ cycle. All the patients received 75% reduced dose of Venetoclax 100 mg instead of 400 mg, as all patients were on azole’s (CYP3A4 inhibitor) as prophylaxis or therapeutic antifungal. Response assessment was done by bone marrow aspirate and biopsy after 1st cycle and 2nd cycle. MRD assessment was also done by eight color flowcytometry on bone marrow aspirate. Adverse events were noted as per Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Results: Between January 2022 to January 2023, 8 patients were treated with HMA plus venetoclax. Baseline characteristics of patient shown in Table 1. After cycle one, 5/8 patients achieved CR +Cri; after cycle 2, 3/8 patients achieved CR+ CRi. In 4/8 patients, MRD was done. Two patients achieved MRD <0.1%, one patient achieved MRD 1.41%, and one patient achieved MRD 0.16%. Common adverse events (Grade≥ 3) observed were thrombocytopenia (n=7), Anemia (n=7) and neutropenia(n=3). Only 2/8 patients had febrile neutropenia. There was no mortality. Summary/Conclusion Irrespective of the risk group, all medically unfit patients achieved complete remission after 1 or 2 cycle of HMA plus Venetoclax without any mortality. So irrespective of medical fitness status, this combination can be explored as induction therapy with reduced mortality compared to standard 3 + 7 regimen followed by consolidation with chemotherapy or bone marrow transplant.Keywords: Minimal residual disease (MRD), Acute myeloid leukemia